Baseline levels of low-density lipoprotein cholesterol and lipoprotein (a) and the AvaII polymorphism of the low-density lipoprotein receptor gene influence the response of low-density lipoprotein cholesterol to pravastatin treatment

• Published in: Metabolism, clinical and experimental Vol. 54; no. 6; pp. 741 - 747
• Main Authors: Lahoz, Carlos, Peña, Rocío, Mostaza, Jose M., Laguna, Fernando, García-Iglesias, María F., Taboada, Manuel, Pintó, Xavier
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2005
• Subjects: Adult; Aged; Cholesterol, LDL - blood; Deoxyribonucleases, Type II Site-Specific - metabolism; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Hypercholesterolemia - genetics; Lipoprotein(a) - blood; Male; Middle Aged; Polymorphism, Genetic; Pravastatin - therapeutic use; Prospective Studies; Receptors, LDL - genetics
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2004.12.020

To investigate some individual and genetic factors that may influence the response of low-density lipoprotein cholesterol (LDL-C) to pravastatin treatment, we recruited 440 subjects with hypercholesterolemia (mean age, 57 years; 43% men) from 21 primary health care centers-outpatient clinics into a prospective, multicentered intervention trial. Pravastatin (20 mg/d) was prescribed for 16 weeks. The main outcome was the percentage variation in LDL-C concentration relative to baseline. Blood analyses and genotyping were performed centrally. The results indicated that LDL-C decreased by 20.5% (range, +21% to −66%) after pravastatin treatment. Baseline concentration of LDL-C (the higher the concentration, the greater the decrease), lipoprotein (a) levels (the lower the concentration, the greater the response), and AvaII polymorphism of the LDL-receptor gene significantly influenced the hypolipemic effect ( P < .001, P = .014, and P = .004, respectively). These 3 factors combined explained 10.6% of the variation in LDL-C response. Age, sex, smoking habit, alcohol consumption, body mass index, and apolipoprotein E genotype had no significant effect on response. We conclude that baseline levels of LDL-C and lipoprotein (a) together with the AvaII polymorphism of the LDL-receptor gene have a significant influence on the LDL-C response to pravastatin treatment in patients monitored in a standard primary health care outpatient clinic setting.